Salinosporamide A (Compound 1) and omuralide (Compound 2) are potent naturally derived substances which inhibit proteasome function with very high selectivity. See references (1), (2), and (3).

Proteasome inhibition offers considerable promise in the therapy of a number of types of cancer and is already used for multiple myelonoma. See reference (4). Several routes have been developed for the syntheses of Compounds 1 and 2. See references (1) and (5). One potential problem with the use of Compounds 1 or 2 as therapeutic agents is their short half-life in solution at pH 7 or in serum (estimated as low as 5-10 min). Because of this potential shortcoming, we have developed a synthesis of the β-lactam—Compound 3, which, to date has been found to be much more stable than the corresponding β-lactone (or either of Compounds 1 and 2).
